The present invention relates to vascular prostheses, and more particularly relates to vascular grafts impregnated with a heparin-containing collagen sealant.
Vascular prostheses, commonly referred to as grafts, are typically used as soft tissue prostheses to replace damaged or diseased portions of blood vessels. During a surgical procedure, a damaged or diseased blood vessel portion may be removed and replaced with a vascular prosthesis. Complications, however, may occur as a result of the implanted prosthesis because of the body's natural tendency to reject foreign matter. More particularly, thrombosis or blood clotting within or upon the prosthesis may occur.
Precautions must be taken to minimize thrombosis and assure the patency of an implanted vascular prosthesis. Ideally, antithrombogenic properties should be imparted to the prosthesis. In addition to antithrombogenic properties, a vascular graft or prosthesis must be flexible and pliable to ensure that the prosthesis bends and flexes with the normal contours of the body into which it is transplanted. Without such flexibility, normal healing and acceptance by the body of the graft may not occur.
Vascular grafts or prostheses must also be porous to promote an ingrowth of tissue within or upon the vascular graft. More particularly, the exterior surface of the vascular prosthesis should include pores large enough to facilitate the entry of connective tissue and connective tissue cells such as fibroblasts, i.e., the ingrowth of the perigraft tissue. Generally, the larger the pore size, the better the ingrowth of the tissue into the wall from the perigraft tissue.
The interior surface should include pores that are not so large as to allow leakage of blood into surrounding tissues but large enough to promote tissue ingrowth. Blood leakage into surrounding tissues increases the likelihood of infection. The more porous the vascular graft substrate, the greater the tendency to hemorrhage during and after implantation.
Much effort has gone into hemostatic control, i.e., reducing the initial high rate of blood seepage into surrounding tissue from highly porous vascular graft substrates during and immediately after surgery. U.S. Pat. Nos. 3,805,301 and 4,047,242, assigned to the assignee of the subject application, disclose synthetic vascular grafts that are sufficiently porous to permit tissue ingrowth and allow firm attachment of a neointimal lining in the graft.
The vascular grafts disclosed within the U.S. Pat. Nos. 3,805,301 and 4,047,242 patents, however require a general procedure for implantation which includes the step of pre-clotting. During pre-clotting, the graft is immersed in the blood of the patient ex-vivo and allowed to stand for a period of time sufficient for clotting the porous substrate. Without the preclotting, excessive bleeding would occur when blood begins to flow into the vascular graft.
Emersion within a patients blood to pre-clot a graft, however, leaves the graft lumen highly thrombogenic due to the presence of a high concentration of thrombin on the intraluminal surface of the vascular graft. As the blood passes the thrombin buildup, the thrombin attracts platelets, forming a thrombus or blood clot that may detract from the graft's patency.
Other attempts to limit hemorrhaging from implanted grafts during and immediately after surgery include impregnating the vascular graft substrate with gelatinous material, such as that described in U.S. Pat. No. 4,747,848. The impregnated graft is then crosslinked by chemically modifying amino groups of the gelatinous molecules so that they will chemically bond to one another. The crosslinked, impregnated graft provides a sealed structure which prevents or controls bleeding. Subsequent to implantation, the gelatinous material is degraded by hydrolysis, slowly increasing the porosity over time and allowing tissue ingrowth to occur.
Collagen is also well known as an agent which is effectively used to impregnate the pores of synthetic grafts in an effort to limit bleeding upon implantation. Collagen is an insoluble fibrous protein that occurs naturally in vertebrates as the chief constituent of connective tissue fibrils. The patency of grafts impregnated with collagen is high. Collagen impregnated within grafts is gradually biodegraded by the body, uncovering pores present in the graft substrate structure to allow for tissue ingrowth and healing. Collagen coatings, however, are known to attract thrombin agents which form thrombosis or blood clots on surfaces treated with collagen. This can potentially lead to occlusion within transplanted grafts, the problem being especially acute in blood vessels having diameters of 10 mm or less.
U.S. Pat. No. 5,197,977, assigned to the assignee of the present invention, discloses a collagen-impregnated vascular graft which is effective in preventing blood leakage and which also does not require additional processing such as preclotting prior to use. The collagen-impregnation also slowly degrades in the body to enable host tissue ingrowth.
The collagen source with which the vascular graft is impregnated is a fibrous dispersion of high purity. The dispersion may also act as a reservoir for the sustained release of drug materials, such as anti-bacterial agents, anti-thrombogenetic agents and anti-viral agents, in an attempt to minimize bacterial infection and thrombosis subsequent to implantation.
Heparin is a chemical agent that prevents the clotting of blood, i.e., an anticoagulant. Conventional techniques for preparing collagen-heparin dispersions typically result in the precipitation of collagen from the collagen dispersion upon the addition of heparin in sufficient quantity to effectively prevent thrombosis upon grafts impregnated thereby. To prepare a graft with collagen using conventional methods therefore allows for only small quantities of heparin to be added to the sealant.
It is therefore an object of the present invention to provide a collagen-heparin dispersion which overcomes the aforementioned problems of the prior art, and method for forming the same.
It is another object of the present invention to provide a collagen-heparin dispersion in ratios of collagen to heparin such that thrombogenic events are minimized resulting from the implantation of a graft treated with the dispersion.
It is still another object of the present invention to provide a synthetic vascular graft which does not require pre-clotting with a patient's blood prior to implantation, and method for forming the same.
It is another object of the present invention to provide a collagen and heparin impregnated synthetic vascular graft that is coated with heparin to prevent thrombus formation and inhibit smooth muscle cell anastomotic hyperplasia after implantation, and method of forming the same.
It is yet another object of the present invention to provide a collagen and heparin impregnated synthetic vascular prosthesis which minimizes blood loss after implantation, and method for forming the same.
It is still another object of the present invention to provide a collagen and heparin impregnated synthetic vascular prosthesis that promotes cell ingrowth and enhances the rate and degree of healing within a patient's body after implantation, and method for forming the same.
It is still a further object of the present invention to provide a collagen and heparin impregnated vascular prosthesis that releases heparin at a sustained or controlled rate when implanted into a patient's body, and method for forming the same.
Still other objects and advantages of the invention will in part be obvious and will in part be apparent from the detailed description of the invention that follows.